7. Project Summary/Abstract Over 30% of adults aged 65 years and older in the US suffer from osteoarthritis (OA). Hip and knee OA are the most common types of OA with an increasing prevalence. Opioid analgesics are often used for patients with moderate to severe symptomatic OA. When non-pharmacologic and pharmacologic treatments are not effective, patients with severe OA may undergo total joint replacement (TJR). Utilization of TJR has dramatically increased over the past decade. Opioids, particularly long-term use, can result in significant side effects including gastrointestinal and cardiovascular events, respiratory depression, fall, fracture, and death. Benefits and harms of short- and long-term opioid use are thus not only an important issue for older patients with OA, but also an area of great public health concern. Furthermore, some evidence suggests potential negative effects of preoperative opioid use on clinical outcomes including pain, stiffness, patient satisfaction, and requirement of additional surgery following TJR. The primary objectives of this proposal are to evaluate patterns of opioid use among OA patients before and after TJR and to assess the effect of opioid use patterns on clinical outcomes and safety events after TJR in a large U.S. population-based cohort of OA patients. The specific aims of this 4-year proposal are: 1) to identify predictors of persistent opioid use and opioid dose escalation in patients after TJR for hip or knee OA and 2) to evaluate effects of opioid use patterns on short- and long-term clinical outcomes and safety following TJR. The proposed study will use data from the Medicare claims database (2009-2013) linked to clinical data and patient-reported outcomes from the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR); FORCE- TJR is an AHRQ-funded, prospective TJR registry of over 30,000 patients from all regions of the U.S. and includes detailed, longitudinal clinical information that are not available in claims databases such as severity of OA, body mass index, pain and functional status before and after surgery. Given the increasing interest in big data and data linkage in clinical research, the linkage between FORCE-TJR and Medicare claims data provides an innovative and important opportunity to conduct high-quality pharmacoepidemiologic study of opioids in patients undergoing TJR. Using innovative and rigorous pharmacoepidemiologic methods and the linkage of two data sources, we will control for confounding by OA severity, comorbidities, medications, and risk factors associated with opioid use, clinical outcomes, and safety events. The results of the proposed study will help provide evidence- based guidance on surgical risk stratification and pain management of these patients before and after TJR.